#079 Blood-Brain Barrier Dysfunction in Alzheimer’s Disease and Dementia | Axel Montagne, Ph.D.
FoundMyFitness
Rhonda Patrick, Ph.D.
4.8 • 5.5K Ratings
🗓️ 28 February 2023
⏱️ 109 minutes
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Summary
Dr. Axel Montagne is a chancellor's fellow and group leader at the UK Dementia Research Institute at the University of Edinburgh Centre for Clinical Brain Sciences. His group aims to understand how, when, and where critical components of the blood-brain barrier become dysfunctional preceding dementia and in the earliest stages of age-related cognitive decline. With this knowledge, they hope to develop precise treatments targeting brain vasculature to protect brain function.
More importantly his work, and that of his colleagues, provide a critical lens through which to view the contributions of vascular dysfunction (or, conversely, vascular health – if we choose to preserve it) as a critical common thread in dementia and neurodegeneration.
In this episode, we discuss:
- (00:00) Introduction to Dr. Axel Montagne
- (11:44) What dementias have in common
- (12:42) The importance of preserving small blood vessels (in the brain)
- (13:38) Changes in the blood-brain barrier in aging that cause "leaking"
- (15:11) Predicting cognitive decline early with biomarkers – an opportunity for intervention?
- (16:32) Why targeting amyloid isn’t enough
- (18:54) The impact of the APOE4 genotype on brain vasculature
- (24:19) The cause of white matter damage in the brain
- (33:47) Why the loss of omega-3 transport affects pericytes
- (35:25) The role of exercise in prevention of blood-brain barrier dysfunction
- (35:45) Why high heart rates during exercise preserve brain function
- (36:49) The role of exercise in preserving vision health
- (40:17) Why leaky vessels damage myelin and the brain
- (45:31) Can you have more than one type of dementia?
- (47:54) Does the breakdown of the blood-brain barrier cause “type 3 diabetes"?
- (54:03) Why omega-3 may prevent detachment of pericytes
- (1:14:35) Why a hepatitis drug restored cognition in APOE4 mice
- (1:19:39) Why blood-brain barrier disruption results in the accumulation of amyloid-beta
- (1:25:14) Why lifetime hypertension increases dementia risk
- (1:37:13) Effects of obesity on blood-brain barrier leakage
Show notes are available by clicking here
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Transcript
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| 0:00.0 | See, if you don't do enough exercise, you start chronically to have some vessels that will |
| 0:05.3 | basically constrict and collapse and disappear, meaning that the surrounding neurons that are here |
| 0:13.5 | and they need oxygen and nutrients and everything from these vessels. If these vessels disappear, |
| 0:20.0 | you're going to lose neurons, right? So exercises, the number one thing, is your prone to go to |
| 0:26.9 | cognitive decline because let's say you have a major genetic risk, but if on top of that, |
| 0:31.4 | you don't exercise, you're going to accelerate as we know from study. And that's one of the biggest |
| 0:37.0 | thing we have to put that, you know, we have to put to the world like, okay, each exercise that |
| 0:43.1 | had no matter what, I mean, if you want to stay healthy in terms of brain function, yeah, no other |
| 0:48.8 | choice. Today's episode asks a simple question. What if we could find some connection or a common thread |
| 0:56.0 | that ties together most dementia? Could we then use that to intervene and ultimately treat or |
| 1:02.4 | prevent dementia? Or what if, even in the most inevitable cases, we could add even 10 or more |
| 1:09.4 | years of healthy cognitive function? Such a radical idea might soon be the new reality, thanks to |
| 1:15.7 | emerging research like that of today's guests, Dr. Axel Montaine. Axel's work brings into sharp |
| 1:22.1 | focus the incredibly important role that a type of vascular dysfunction, the breakdown of the |
| 1:28.3 | blood brain barrier plays in dementia. Alzheimer's disease is usually more defined by its well-known |
| 1:34.3 | hallmarks, amyloid, and tal. Yet it's in the earliest stages of the cognitive decline, particularly |
| 1:41.2 | among apoe4 carriers, that the microvascular of the brain begins to leak. The fact that these |
| 1:47.9 | vascular issues play such an early part in Alzheimer's might come as a surprise since unlike vascular |
| 1:55.2 | dementia, the clinical focus for Alzheimer's disease has up until now been mostly on amyloid. Yet in |
| 2:03.2 | the pursuit of treatment, it's the targeting amyloid and tal that's seen at best mixed but more |
| 2:10.8 | often downright disappointing results. Nor is Alzheimer's the only disease affected by the failings of |
| 2:17.6 | the brain's microvascular and progressive leakiness of the blood brain barrier. In fact, this degeneration |
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